Nausea and vomiting compromise the health and quality of life of patients with a variety of diseases, and create an obstacle to compliance with treatments that produce these disturbing side effects. Nausea and vomiting can be triggered by appropriate stimulation of several sites in the body, including the gastrointestinal tract and area postrema in the brainstem. The purpose of this project is to determine whether emetic agents and mediators also act in liver to generate a neural signal that triggers vomiting (emesis). Using the ferret, a standard animal model for studies the emetic reflex, we will: (1) Determine whether cyclophosphamide, which is used in cancer chemotherapy, acts in liver to induce emesis by comparing the effects of hepatic portal and jugular (systemic) infusion of different doses of this drug. (2) Determine whether the emetic mediator, 5-hydroxytryptamine (5HT) acts in liver to induce vomiting by comparing the effects of hepatic portal and jugular infusion of different concentrations of 5HT. (3) Investigate whether vagal sensory neurons transmit a hepatic signal for emesis by severing the nerves between the liver to brain. The results of this work should contribute to our knowledge of the mechanisms of nausea and vomiting, and may lead to the development of better treatments for these conditions.